P782: IMMUNOPHENOTYPIC AND MOLECULAR GENETIC MARKERS OF UNFAVORABLE PROGNOSIS IN PATIENTS WITH MYELODYSPLASTIC SYNDROME
Authors: H. Trubkina, I. Iskrou, V. Smolnikova, T. Lebedeva, I. Lendzina
Journal: HemaSphere (2022)

Background: Therapy is selected based on risk, need for transfusion of blood components, percentage of bone marrow blasts, and cytogenetic profile. In low-risk groups, the goal of treatment is to reduce the need for replacement therapy and prevent transformation to higher-risk or AML. In higher risk groups, the goal is to prolong survival. Currently, there are no approved criteria for selecting therapy for patients with MDS based on the classifications and prognostic scales used, treatment regimens for progression of MDS or its refractory forms. Aims: The aim of the study was to identify unfavorable prognostic immunophenotic and molecular genetic markers of blast cells in patients with high-risk myelodysplastic syndrome Methods: The prospective cohort study included 68 patients with newly diagnosed MDS in the period from January 2017 to December 2021. The patients underwent a primary diagnostic complex of MDS, including immunophenotyping and molecular genetic research of bone marrow aspirate. The age of patients is 25-82 years, the median age is 64 years. According to the IPSS classification included: high risk (10 pats), intermediate-2 (26 pats), intermediate-1 (26 pats), low risk (6 pats). According to the IPSS-R classification included: very high risk (23 pats), high risk (17 pats), intermediate (14 pats), low risk (12 pats), very low risk (2 pats). The following molecular genetic markers were found: complex aberrations >3 (10 pats), trisomy 8 chromosome (8 pats), absence of molecular genetic disorders (27 pats), isolated 5q chromosome (13 pats), any changes of the 7 chromosome (8 pats), deletion of the 20 chromosome (3 pats), deletion of the 11 chromosome (1 pats), TP53 (2 pats). To explore immunophenotic and molecular genetic markers we use three state “illness-death” model. We consider the following states: diagnosis, transformation into leukemia; death. Results: We identified high-risk immunophenotypic and molecular genetic markers - · for transition “diagnosis-death”: - CD38 <50% HR 3.7 (1.2-11.5 CI; p = 0.022), - CD13> 50% HR 8.7 (1.1-67.8 CI; p = 0.04), - complex aberrations >3 HR 5.8 (1.4-24.6 CI; p=0,015); - · for transition “diagnosis-transformation”: - CD71 ≥65% HR 4.1 (1.35-12.4 CI; p = 0.013); - CD13> 75% HR 2.8 (1.1-7.1 CI; p = 0.034), - complex aberrations >3 HR 2.8 (0,86-9,0 CI; p=0,087); - · for transition “transformation-death“: - CD25 <5% HR 6.3 (1.4-28 / 4 CI; p = 0.017), - CD 33 <50% HR 6.6 (1.3-34.7 CI; p = 0.026)), - complex aberrations >3 HR 0,22 (0,06-0,84 CI; p=0,027), - trisomy 8 chromosome HR 7.9 (0.71-88 CI; р=0,093). Figure 1 – The probability of various conditions depending on the time since the diagnosis. State 1 - estimation of the probability of being in the state «diagnosis-transformation» State 2 - estimation of the probability of being in the state «transformation-death» State 3 - estimation of the probability of being in the state «diagnosis-death» Image:Summary/Conclusion: The selection of groups of patients with identified immunophenotypic and molecular genetic markers of a high risk of transformation into acute leukemia and a high risk of death (“diagnosis-death”: CD38<50%, CD13>50%, complex aberrations>3; “diagnosis-transformation”: CD71≥65%, CD13>75%, complex aberrations>3; “transformation-death“: CD25<5%, CD33<50%, complex aberrations>3, trisomy 8 chromosomes) requires consideration of a new approach to therapy.